The renin-angiotensin-aldosterone system normally functions as a homeostatic regulator of electrolyte composition, volume and blood pressure. We are studying abnormalities of this system as expressed clinically in disorders of electrolyte and acid-base metabolism and hypertension in man. A syndrome of primary renin deficiency (hyporeninemic hypoaldosteronism) commonly results in clinically significant hyperkalemia and metabolic acidosis in patients with chronic renal disease. Extensive metabolic balance studies have been undertaken to further characterize the role of mineralocorticoid hormones in the adaptation to the progressive loss of nephron function in man. A selective renal venous catheterization technique is utilized to detect localized hypersecretion of renin in hypertensive patients with lesions affecting a portion of the kidney. The diagnostic value of an angiotensin converting enzyme inhibitor and the therapeutic role of beta-blockers are being evaluated in this patient population. Primary abnormalities in renal electrolyte transport and the modifying effect of secondary increases in activity of the renin-aldosterone system are being studied in patients with disorders associated with renal potassium wasting. The role of adrenal mineralocorticoids as a cause of hypertension is being studied using a rat kidney receptor assay. Particular attention is directed to patients with low-renin essential hypertension, to determine the likelihood that mineralocorticoids are playing a causative role in their hypertension.